This proposal is a developmental study of the mechanisms by which premature separation of the young rat from its mother produces a subsequent increase in restraint-induced erosion susceptibility. Work in this laboratory has shown that premature maternal separation increases the incidence of restraint erosions in young rats from 20% (normal controls) to 70-90%. Premature loss of maternal milk is the key factor at the time of separation; and a disturbance in body temperature regulation is one of the key consequences at the time of restraint stress. Whether this temperature disturbance is also part of the pathophysiology of erosion formation is not yet known, although we have shown that it is closely linked to the regulation of acid secretion. The proposed experiments are intended to elucidate these phenomena further. Some of the studies will focus on the relations between body temperature regulation, gastric physiology and the pathophysiology of restraint-induced gastric erosions. Other studies will focus on clarifying the nature of the (presumably central thermoregulatory disturbance itself. And still other studies will focus on the recent observation from this laboratory that premature separation of female rats also increases the risk of restraint erosions in their normally reared progeny. In all of the studies, the strategy will be to compare prematurely weaned (high risk) and normally weaned (low risk) rats to determine factors which differentiate them. These factors will then be studied in analytic experiments to determine which are specifically relevant to erosion pathogenesis, and how they are relevant.